1. B cell lipid rafts regulate both peptide-dependent and peptide-independent APC-T cell interaction.
- Author
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Setterblad N, Bécart S, Charron D, and Mooney N
- Subjects
- Actins physiology, Animals, Antigen Presentation drug effects, Antigen-Presenting Cells ultrastructure, B-Lymphocytes drug effects, B-Lymphocytes ultrastructure, CD4 Antigens genetics, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes ultrastructure, Cell Communication, Cells, Cultured immunology, Cells, Cultured ultrastructure, Cyclodextrins pharmacology, Cytoskeleton physiology, Enzyme Inhibitors pharmacology, HLA-DR Antigens immunology, HLA-DRB1 Chains, Humans, Hybridomas immunology, Hybridomas ultrastructure, Interleukin-2 metabolism, Lymphocyte Activation, Macromolecular Substances, Mice, Protein Kinase C antagonists & inhibitors, Protein Kinase C physiology, Recombinant Fusion Proteins immunology, Signal Transduction, T-Cell Antigen Receptor Specificity, Tetanus Toxoid immunology, Antigen Presentation physiology, Antigen-Presenting Cells immunology, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology, Intercellular Junctions immunology, Membrane Microdomains physiology, Peptide Fragments immunology, beta-Cyclodextrins
- Abstract
Formation of an immunological synapse (IS) between APCs and T CD4(+) lymphocytes is a key event in the initiation and the termination of the cognate immune response. We have analyzed the contribution of the APC to IS formation and report the implication of the actin cytoskeleton, the signaling proteins and the lipid rafts of B lymphocytes. Recruitment of MHC class II molecules to the IS is concomitant with actin cytoskeleton-dependent B cell raft recruitment. B cell actin cytoskeleton disruption abrogates both IS formation and T cell activation, whereas protein kinase C inhibition only impairs T cell activation. Pharmacological B cell lipid raft disruption inhibited peptide-dependent T lymphocyte activation and induced peptide-independent but HLA-DR-restricted APC-T cell conjugate formation. Such peptide-independent conjugates did not retain the ability to activate T cells. Thus, B cell lipid rafts are bifunctional by regulating T cell activation and imposing peptide stringency. more...
- Published
- 2004
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